Integrin signaling via FAK-Src controls cytokinetic abscission by decelerating PLK1 degradation and subsequent recruitment of CEP55 at the midbody
| Autor: | Deepesh Kumar Gupta, Staffan Johansson, Ying Huang, Rajesh Kumar Gupta, Siamak A. Kamranvar |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Integrins Cell division integrin Integrin Fluorescent Antibody Technique Cell Cycle Proteins cytokinesis Protein Serine-Threonine Kinases Biology ESCRT Cell Line 03 medical and health sciences 0302 clinical medicine Abscission Proto-Oncogene Proteins Cell Adhesion Humans CEP55 Cell adhesion Endosomal Sorting Complexes Required for Transport FAK Calcium-Binding Proteins Nuclear Proteins Fibroblasts G1 Phase Cell Cycle Checkpoints Extracellular Matrix Cell biology DNA-Binding Proteins Midbody src-Family Kinases 030104 developmental biology Oncology Focal Adhesion Protein-Tyrosine Kinases Proteolysis Cancer cell biology.protein PLK1 030217 neurology & neurosurgery Cytokinesis Protein Binding Signal Transduction Transcription Factors Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Siamak A. Kamranvar 1 , Deepesh Kumar Gupta 1 , Ying Huang 1 , Rajesh Kumar Gupta 2 , Staffan Johansson 1 1 Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden 2 Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden Correspondence to: Siamak A. Kamranvar, e-mail: siamak.kamranvar@imbim.uu.se Staffan Johansson, e-mail: staffan.johansson@imbim.uu.se Keywords: cytokinesis, CEP55, PLK1, integrin, FAK Received: October 31, 2015 Accepted: April 09, 2016 Published: April 26, 2016 ABSTRACT Adhesion to extracellular matrix is required for cell cycle progression through the G1 phase and for the completion of cytokinesis in normal adherent cells. Cancer cells acquire the ability to proliferate anchorage-independently, a characteristic feature of malignantly transformed cells. However, the molecular mechanisms underlying this escape of the normal control mechanisms remain unclear. The current study aimed to identify adhesion-induced reactions regulating the cytokinesis of non-transformed human fibroblasts. The adhesion-dependent control of cytokinesis was found to occur at a late stage close to the abscission, during which the endosomal sorting complex required for transport (ESCRT) severs the thin intercellular bridge connecting two nascent daughter cells. CEP55, a key protein involved in the abscission process, was localized at the midbody in both adherent and non-adherent fibroblasts, but it was unable to efficiently recruit ALIX, TSG101, and consequently the ESCRT-III subunit CHMP4B was missing in the non-adherent cells. PLK1, a kinase that prevents premature recruitment of CEP55 to the midbody, disappeared from this site more rapidly in the non-adherent cells. A FAK-Src signaling pathway downstream of integrin-mediated cell adhesion was found to decelerate both PLK1 degradation and CEP55 accumulation at the midbody. These data identify the regulation of PLK1 and CEP55 as steps where integrins exert control over the cytokinetic abscission. |
| Databáze: | OpenAIRE |
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